Identification of serological markers of protection and risk for dengue vaccines and natural infection
鉴定登革热疫苗和自然感染的保护和风险的血清学标记
基本信息
- 批准号:10638037
- 负责人:
- 金额:$ 69.11万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-15 至 2027-07-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAntibodiesAntibody ResponseAntibody-Dependent EnhancementAntigenic SpecificityAntigenic VariationAttenuatedAutomobile DrivingB-LymphocytesBiologicalBiological AssayCollectionComplement ActivationCountryDengueDengue InfectionDengue VaccineDengue VirusDengvaxiaDevelopmentDimensionsDiseaseEffectivenessEvaluationFailureGrantHumanImmuneImmune responseImmunityImmunologic MarkersImmunological ModelsImmunologicsImmunology procedureIndividualInfectionLabelLicensingLicensureLife Cycle StagesLinkLongterm Follow-upMeasuresMediatingMemoryMemory B-LymphocyteModelingOutcomeParticipantPerformancePeripheral Blood Mononuclear CellPhilippinesPopulationPublic HealthRecording of previous eventsRiskRisk AssessmentRisk MarkerRoleSafetySamplingSeveritiesSeverity of illnessSystemT cell responseT-LymphocyteThailandTimeUnited States National Institutes of HealthVaccinatedVaccinationVaccineeVaccinesWorkantibody-dependent cell cytotoxicitycohortdesigndisorder riskepidemiology studyexperiencefollow-upimmunological diversityimprovedinfection riskmathematical modelpathogenphase 3 testingrecruitresponseserological markerunvaccinatedvaccine candidatevaccine developmentvaccine evaluationvaccine trial
项目摘要
Project Summary
Dengue remains stubbornly endemic in many countries. Vaccine development efforts have been hampered by
a poor understanding of the immune response. We do know that pre-existing immunity from vaccination or
historic infections is key to driving disease risk, however, accurate markers of risk or protection are lacking,
including how they change over multiple years. Less is known about the role of non-neutralizing antibody
functions, such as antibody-dependent cell cytotoxicity, and antibody-dependent enhancement in driving disease
risk. Neutralizing and non-neutralizing antibody responses have not been characterized alongside cellular
immune responses that have been identified to be associated with risk of illness. Here, we will expand upon
previous work on the diversity of neutralization responses to specifically add characterization of non-neutralizing
antibody responses and cellular immune responses from natural infection and vaccination using samples taken
from the same individuals over numerous time points. These samples come from cohorts that had regular
collection of sera and PBMC and were followed for instances of infection and illness, many of which severe. This
includes a cohort of individuals that were vaccinated by the only licensed dengue vaccine, a cohort followed for
13 years. We also have access to samples from individuals vaccinated with another candidate vaccine followed
over five years. Finally, we will re-recruit cohort participants to provide samples 23 years after their participation
to investigate long term responses after infections. We will measure multiple non-neutralizing and neutralizing
responses to a diverse set of dengue viruses a wide range of antibody measures as well as a limited set of
cellular immune responses, providing a multi-dimensional, systems characterization of humoral and cellular
immune responses. We will use this multi-dimensional measure and mathematical models to reconstruct full
infection histories and immune dynamics. These efforts will provide a set of correlates of protection/risk of illness
and infection that can be used to assess risk in vaccine trials and epidemiological studies. These mechanistic
models will be generally useful to infer dynamics of immune responses to antigenically variable pathogens and
can be used to assist in the design and analysis of vaccine trials and epidemiological studies.
Relevance to Public Health
Multiple candidate dengue vaccines are currently in development, however, their likely effectiveness over short
and long time periods remain unknown due to a lack of good markers of protection or risk. Identifying such
markers, and how they change over time is critical to their optimal use, continued efficacy and population safety.
More broadly, characterization of non-neutralizing antibody and cellular immune responses to a diverse set of
dengue viruses alongside neutralizing responses in humans followed over many years who have experienced
dengue infection and/or vaccination will increase our understanding of immune responses to dengue.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Derek A Cummings其他文献
Derek A Cummings的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Derek A Cummings', 18)}}的其他基金
Human mobility models to forecast disease dynamics and the effectiveness of public health interventions
用于预测疾病动态和公共卫生干预措施有效性的人员流动模型
- 批准号:
10390412 - 财政年份:2021
- 资助金额:
$ 69.11万 - 项目类别:
Human mobility models to forecast disease dynamics and the effectiveness of public health interventions
用于预测疾病动态和公共卫生干预措施有效性的人员流动模型
- 批准号:
10599117 - 财政年份:2021
- 资助金额:
$ 69.11万 - 项目类别:
Human mobility models to forecast disease dynamics and the effectiveness of public health interventions
用于预测疾病动态和公共卫生干预措施有效性的人员流动模型
- 批准号:
10228957 - 财政年份:2021
- 资助金额:
$ 69.11万 - 项目类别:
LINKING ANTIGENIC & GENETIC VARIATION OF DENGUE TO INDIVIDUAL AND POPULATION RISK
连接抗原
- 批准号:
8801344 - 财政年份:2015
- 资助金额:
$ 69.11万 - 项目类别:
Modeling interactions between HIV interventions in key populations in India
模拟印度重点人群艾滋病毒干预措施之间的相互作用
- 批准号:
8846213 - 财政年份:2015
- 资助金额:
$ 69.11万 - 项目类别:
LINKING ANTIGENIC & GENETIC VARIATION OF DENGUE TO INDIVIDUAL AND POPULATION RISK
连接抗原
- 批准号:
9012767 - 财政年份:2015
- 资助金额:
$ 69.11万 - 项目类别:
LINKING ANTIGENIC & GENETIC VARIATION OF DENGUE TO INDIVIDUAL AND POPULATION RISK
连接抗原
- 批准号:
9269963 - 财政年份:2015
- 资助金额:
$ 69.11万 - 项目类别:
Monitoring cause-specific school absences to estimate influenza transmission in W
监测特定原因的学校缺勤以估计西澳的流感传播情况
- 批准号:
8728607 - 财政年份:2013
- 资助金额:
$ 69.11万 - 项目类别:
Monitoring cause-specific school absences to estimate influenza transmission in W
监测特定原因的学校缺勤以估计西澳的流感传播情况
- 批准号:
9381264 - 财政年份:2013
- 资助金额:
$ 69.11万 - 项目类别:
Monitoring cause-specific school absences to estimate influenza transmission in W
监测特定原因的学校缺勤以估计西澳的流感传播情况
- 批准号:
8632337 - 财政年份:2013
- 资助金额:
$ 69.11万 - 项目类别:
相似海外基金
University of Aberdeen and Vertebrate Antibodies Limited KTP 23_24 R1
阿伯丁大学和脊椎动物抗体有限公司 KTP 23_24 R1
- 批准号:
10073243 - 财政年份:2024
- 资助金额:
$ 69.11万 - 项目类别:
Knowledge Transfer Partnership
Role of Natural Antibodies and B1 cells in Fibroproliferative Lung Disease
天然抗体和 B1 细胞在纤维增生性肺病中的作用
- 批准号:
10752129 - 财政年份:2024
- 资助金额:
$ 69.11万 - 项目类别:
CAREER: Next-generation protease inhibitor discovery with chemically diversified antibodies
职业:利用化学多样化的抗体发现下一代蛋白酶抑制剂
- 批准号:
2339201 - 财政年份:2024
- 资助金额:
$ 69.11万 - 项目类别:
Continuing Grant
Isolation and characterisation of monoclonal antibodies for the treatment or prevention of antibiotic resistant Acinetobacter baumannii infections
用于治疗或预防抗生素耐药鲍曼不动杆菌感染的单克隆抗体的分离和表征
- 批准号:
MR/Y008693/1 - 财政年份:2024
- 资助金额:
$ 69.11万 - 项目类别:
Research Grant
Discovery of novel nodal antibodies in the central nervous system demyelinating diseases and elucidation of the mechanisms through an optic nerve demyelination model
发现中枢神经系统脱髓鞘疾病中的新型节点抗体并通过视神经脱髓鞘模型阐明其机制
- 批准号:
23K14783 - 财政年份:2023
- 资助金额:
$ 69.11万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Elucidation of the mechanisms controlling the physicochemical properties and functions of supercharged antibodies and development of their applications
阐明控制超电荷抗体的理化性质和功能的机制及其应用开发
- 批准号:
23KJ0394 - 财政年份:2023
- 资助金额:
$ 69.11万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Developing first-in-class aggregation-specific antibodies for a severe genetic neurological disease
开发针对严重遗传神经系统疾病的一流聚集特异性抗体
- 批准号:
10076445 - 财政年份:2023
- 资助金额:
$ 69.11万 - 项目类别:
Grant for R&D
PLA2G2D Antibodies for Cancer Immunotherapy
用于癌症免疫治疗的 PLA2G2D 抗体
- 批准号:
10699504 - 财政年份:2023
- 资助金额:
$ 69.11万 - 项目类别:
Genetic adjuvants to elicit neutralizing antibodies against HIV
基因佐剂可引发抗艾滋病毒中和抗体
- 批准号:
10491642 - 财政年份:2023
- 资助金额:
$ 69.11万 - 项目类别:
Novel Immunogens to Elicit Broadly Cross-reactive Antibodies That Target the Hemagglutinin Head Trimer Interface
新型免疫原可引发针对血凝素头三聚体界面的广泛交叉反应抗体
- 批准号:
10782567 - 财政年份:2023
- 资助金额:
$ 69.11万 - 项目类别: